Escherichia coli infections in poultry and animals have become a global problem. Currently, little is known regarding the epidemiology of extended-spectrum beta-lactamases (ESBLs) producing Escherichia coli in infected poultry and cattle. This study aimed to identify antibiotic resistance patterns and ESBL-producing genes in E. coli strains recovered from diseased poultry and animals in northern Egypt. A total of 100 consecutive, no duplicate clinical samples from diseased broiler poultry and 50 samples from diseased cattle were collected during a one-year period. ESBL was found in 44% (24 out of 54) isolates of E. coli isolated from infected poultry positive for double disc diffusion, and 66% (16 out of 24) isolates of E. coli recovered from cattle positive for double disc diffusion. ESBL genes (blaCTX-M1, blaCTX-M2, blaOXA10, blaSHV, blaTEM, blaOXA-2, blaVEB, blaPER-2, and blaGES) were detected in strains by multiplex polymerase chain reaction with gene-specific primers. From 40 phenotypically positive ESBL isolates, we discovered that blush, blaTEM, blactx-m1, and blactx-m9 (100%) were the most prevalent genotypes in cattle isolates, whereas blaGes and blactx-m9 (70% of isolates from poultry). This is the first study to look at ESBL resistance patterns and ESBL-producing genes in E. coli isolated from poultry and cattle. Our analysis found varying occurrences among isolates from various hosts.